Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients.
Mujdat ZeybelOzlem AltayMuhammad ArifXiangyu LiHong YangClaudia FredoliniMurat AkyildizBurcin SaglamMehmet Gökhan GönenliDilek UralWoonghee KimJochen M SchwenkCheng ZhangSaeed ShoaieJens B NielsenMathias UhlénJan BorénAdil MardingluPublished in: Molecular systems biology (2022)
Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMAs) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria, and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomic data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.
Keyphrases
- end stage renal disease
- oxidative stress
- newly diagnosed
- uric acid
- chronic kidney disease
- adipose tissue
- prognostic factors
- peritoneal dialysis
- stem cells
- randomized controlled trial
- metabolic syndrome
- dna damage
- squamous cell carcinoma
- cell death
- body mass index
- insulin resistance
- nitric oxide
- machine learning
- artificial intelligence
- signaling pathway
- big data
- endoplasmic reticulum stress
- single cell
- electronic health record
- rectal cancer
- weight gain
- locally advanced